The overall goals of this program are the elucidation of the biological properties of the major histocompatiblity complex (HLA); its role in immunoregulation and relation to disease susceptibility. Identification and characterization of histocompatibility determinants coded for by the known loci of HLA (A,B,C, and D) and identification of other alloantigens and genetic traits coded for by the HLA-linkage group will increase the quality of histocompatibility testing and subsequently result in improvement in clinical transplantations. This program focuses on the study of histocompatibility determinants in normal individuals and in different patient populations. The individual projects of the program emphasize: 1. The complexity of the HLA-D genetic region (which governs the lymphocyte activation in the mixed lymphocyte culture reaction) and the genetic control of alloantigens selectively expressed on B-lymphocytes (DR determinants); 2. analysis of the genetic control of generation of cytotoxic lymphocytes and lymphocytes with specific immunological memory in allogeneic in vitro reactions; 3. definition of the distribution of restricted alloantigens on lymphoid subpopulations and the study of the functional characteristics of these lymphocytes in order to identify their role in immunoregulation; and 4. the study of associations between histocompatibility determinants and diseases.